You probably haven’t heard about the ketogenic diet. It hasn’t garnered the media attention like Atkin’s, South Beach, or Paleo. The ketogenic diet, however, has been around since the 1920s, and is one those in the ME/CFS and Fibro community might want to get to know.

First popularized in the 1920s as an effective treatment for intractable epileptic seizures, the diet is still used today for epileptics who fail medications. It has also been widely studied as an adjuvant in cancer and other neurological disorders such as Parkinson’s, ALS, and Alzheimer’s. A Cochrane meta-analysis highlighted the safety and effectiveness of this diet for controlling seizures (1).

Implementing a ketogenic diet is quite different than other big-name diet plans. To become “keto-adapted,” the dieter must flip a switch on their metabolism. Instead of burning carbohydrates (glucose) for fuel, the cells must switch over to burning fats in the form of ketones. The downside of burning carbohydrates as fuel, is the production of cellular stress and free radicals. Ketones provide a “cleaner” energy for cells and are less damaging to cell membranes. This could be compared to a car burning diesel (carbohydrate) versus a car burning unleaded gasoline (ketones).

This is not to say glucose is completely absent in someone who is keto-adapted. Dietary protein can also be a source of glucose for vital organs that require constant supply, such as the brain. Too much protein, however, can cause blood sugar surges that stimulate insulin and “undo” the keto-adapted state.

A ketogenic diet can be initiated with a 12-72 hour fast. Then the diet is maintained by consuming 75-90% of calories as fat, with the remainder coming from moderate amounts of protein and very little carbohydrate.

The ketogenic diet should be considered when dealing with ME/CFS, and perhaps even Fibromyalgia. A body of research in animals and humans have highlighted some of the mechanisms by which dietary ketones promote cellular health.

Here I highlight 3 compelling reasons why the ME/CFS and fibro community should get to know ketosis.

A Ketogenic Diet is Good for Mitochondria

By their very nature as ATP-churning, energy machines, mitochondria produce an enormous quantity of free radicals. These radicals must be “quenched” by antioxidants to reduce the damage to the delicate organelle’s scaffolding. Glutathione, selenium, coQ10, and others play a key role in combating the free radical onslaught.

Mitochondrial dysfunction is widely recognized as a contributor to ME/CFS and Fibromyalgia symptoms. Indeed, many studies have determined that patients have depleted antioxidants, leaving mitochondria particularly vulnerable (2,3).

Ketogenic diets have been found to reduce free radical damage and thereby improve mitochondrial function. Also, ketogenic diets have been found to increase glutathione synthesis--the most important antioxidant for the mitochondria (5). In a recent study, fibroblasts from fibromyalgia patients were found to have decreased mitochondria per cell. When patients were given the metabolic drug metformin and prescribed caloric restriction (a means to achieve ketosis) the fibroblasts showed a more resilient response to free radical damage (4).

A Ketogenic Diet is Good for the Immune System

New studies are emerging demonstrating the role of ketosis in regulating the immune system. In animal models, a 72-hour fast that increases blood ketones, stimulates hematopoetic stem cells. These are cells that will differentiate into various types of white blood cells (6). 

A blockbuster ME/CFS study is now underway studying the effects of the B-cell depleting drug Rituximab (7). This cancer drug may provide relief for a subset of patients through similar mechanisms as ketosis—out with the dysfunctional immune cells, in with new. Rituximab has also been studied in autoimmune diseases such as RA. Fasting studies in RA patients demonstrated reduced joint pain and inflammation, which suggests a similar mechanism (10).

Promoting a ketogenic state during the use of Rituximab may make the drug better tolerated and promote a more robust immune response. Ketogenic diets, achieved through fasting, are being studied as a cancer adjuvant to lessen the toxic effects of traditional chemotherapy in various cancers (10).

A Ketogenic Diet May Reduce Neuroinflammation

The topic of neuroinflammation in ME/CFS is starting to gain traction as new research emerges. A Japanese group detected neuroinflammation on PET imaging (8). Newcomer Jarred Younger detected high levels of the pro-inflammatory molecule leptin in a cohort of patients (9). The effects of leptin occur in the brain and may promote “sickness behavior,” or more commonly, malaise. Animal models of ME/CFS have also demonstrated neuroinflammation driven by inflammatory antiviral molecules, like IFNγ. Increased IFNγ has been a consistent, yet non-specific, finding among ME/CFS research (2).

Ketones have demonstrated their ability to down regulate IFNγ and reduce leptin (10). Other pro-inflammatory cytokines have been shown to reduce in a ketotic state; IL-6 and IL-1β. Finally, ketogenic diets increase the production of BDNF in the brain, which stimulates neuronal stem cells and repairs damaged neuronal connections--a potential perpetrator of the dreaded brain fog (10).

Summary of Ketogenic Diet Effects:

• Increases glutathione production

• Increases BDNF gene expression

• Increases mitochondria concentration

• Stimulates hematopoietic stem cells

• Reduces inflammatory molecules (leptin, IFNγ, IL-6, IL-1β)

• Reduces oxidative stress in the mitochondria

References 

1  Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2012 Mar 14;3:CD001903. http://www.ncbi.nlm.nih.gov/pubmed/22419282

2  Maes, M, et al. Increased plasma peroxides as a marker of oxidative stress in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Med Sci Monit. 2011 Apr;17(4):SC11-5. http://www.ncbi.nlm.nih.gov/pubmed/21455120

3  Cordero MD, et al. Oxidative stress and mitochondrial dysfunction in fibromyalgia. Neuro Endocrinol Lett. 2010;31(2):169-73. http://www.ncbi.nlm.nih.gov/pubmed/20424583

4  Alcocer-Gómez E, et al. Metformin and caloric restriction induce an AMPK-dependent restoration of mitochondrial dysfunction in fibroblasts from Fibromyalgia patients. Biochim Biophys Acta. 2015 Mar 14. pii: S0925-4439(15)00069-1. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/25779083

5  Swann JW. How Does the Ketogenic Diet Work? Epilepsy Curr. 2004 Jan;4(1):20-21. http://www.ncbi.nlm.nih.gov/pubmed/15346140

6  Cheng CW, et al. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014 Jun 5;14(6):810-23. http://www.ncbi.nlm.nih.gov/pubmed/24905167

7  Fluge Ø, et al. Benefit from B-lymphocyte depletion using the anti-CD20 antibody rituximab in chronic fatigue syndrome. A double-blind and placebo-controlled study. PLoS One. 2011;6(10):e26358. http://www.ncbi.nlm.nih.gov/pubmed/22039471

8  Nakatomi Y, et al. Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. J Nucl Med. 2014 Mar 24;55(6):945-950. http://www.ncbi.nlm.nih.gov/pubmed/24665088

9  Stringer EA, et al. Daily cytokine fluctuations, driven by leptin, are associated with fatigue severity in chronic fatigue syndrome: evidence of inflammatory pathology. J Transl Med. 2013 Apr 9;11:93. http://www.ncbi.nlm.nih.gov/pubmed/23570606

10  Longo VD & Mattson MP. Fasting: molecular mechanisms and clinical applications. Cell Metab. 2014 Feb 4;19(2):181-92. http://www.ncbi.nlm.nih.gov/pubmed/24440038